As is well known, VEGF tumor vasculature, which is driven by tumor hypoxia, differs significantly from vasculature found in normal blood vessels. Importantly, tumor VEGF vasculature results in significant gaps between individual tumor endothelial cells, which is much larger than gaps between healthy endothelial cells. This difference allows for nanoparticle targeting of tumor tissue.
Nanoparticles of a diameter of greater than 40 nm cannot enter normal tissue because the gap between healthy endothelial cells is too small. However, nanoparticles of a diameter of between 60 and 400 nm selectively penetrate tumor tissue regions because the gap between individual tumor endothelial cells is large enough to allow for entry. Nanoparticles large enough for selective tumor tissue penetration (diameter of between about 60 and about 400 nm) cannot be localized internally by tumor cells through pinocytosis, which is limited to particles of a diameter of less than about 20 nm. Accordingly, nanoparticles which can selectively penetrate tumor tissue release the chemotherapeutic payload extracellularly through degradation of the polymer matrix, which results in unselective delivery of the active ingredient.
Thus, what is needed are nanoparticles large enough for selective tumor tissue penetration (diameter of between 60 and 400 nm) which can decompose within the tissue to a size amenable for cellular uptake (diameter of less than about 20 nm) by tumor cells. The above concept may have broad app beyond selective delivery of active ingredients to tumor tissues.